The NYU Lung Cancer Biomarker Center conducts lung cancer screening of Con Edison utility workers and others with >20 pack-years smoking [unreadable] asbestos exposure, with spiral CT scans, induced sputum, respiratory questionnaires, pulmonary function tests (PFTs), and blood. Over 1200 have completed the survey. 73% are >51 years;there are equal numbers of men and women;11% are minority;and 70% smoked >30 years. On CT scans, 50% had solid nodules, 10% ground-glass opacities, 5% pleural plaques,and 5% fibrosis. Eight lung cancers were diagnosed. 69% had an obstructive pattern on their PFTs. We have enrolled 111 rule-out lung cancer patients and 60% were diagnosed with adenocarcinomas. We have identified a unique microarray pattern of lung preneoplasia (atypical adenomatous hyperplasia) with differential expression of Rab and Wnt pathways. M.-s. Tang has identified K-ras exon 1 codon 12 DNA adducts in NHBE cells that are poorly repaired and showed that cigarette smoke metals interfere with DNA repair. EDRN collaborations are ongoing with circulating DNA methylation, bronchoalveolar lavage and serum proteomics, antibody arrays to lung cancer antigens, and ELISAs to serum antigens. In the next five years we will evaluate an additional 1000 smokers, obtain 250 lung cancers, and screen 200 nonsmoking controls. Phase II studies will be done on 1) K-ras mutations, adducts, and DNA repair in lung cancer, adjacent uninvolved tissue, bronchial brush, and PBMCs (with M.-s. Tang);2) serum S-adenosyl methionine, a methylation intermediate (with S. Merali);3) matrix protein arrays (with Milagen);4) MR quantification of perfusion in lung cancer versus nodules (with J. Ko);and 5) comparing serum proteomics of ovarian versus lung adenocarcinoma (with D. Fishman). D. Fishman directs the Women's Cancer Center, providing access to 20,000 new screening registrants. The New York Cancer Project Biorepository Facility will now process and store our blood specimens;they have 20,000 enrollees under prospective follow-up. J. Goldberg provides study design, programming, and biostatistical support to ensure the high quality of our data processing. Large patient cohorts plus diversity of biomarker phase II studies will result in accelerated translation of feasible lung cancer biomarkers to complement single-breath CT scanning.